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Adipose tissue varies depending on localization. Vijay et al. perform single-cell RNA sequencing in multiple adipose tissue depots from obese individuals and identify distinct subpopulations of endothelial cells, immune cells and pre-adipocytes.
Amyloid precursor protein contributes to the pathogenesis of Alzheimer’s disease. An et al. show that its increase in white adipose tissue under a high-fat diet promotes obesity and impairs mitochondrial function by blocking the protein import machinery.
Bevers and Litovchenko et al. sequence mitochondrial genomes from 169 different inbred Drosophila melanogaster strains to reveal mitochondrial population structure as well as links between mitochondrial haplotypes and metabolic variation in flies.
Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.
Known as a regulator of lipolysis, ABHD5 is found to also act as a serine protease that cleaves HDAC4 in response to catecholaminergic stimulation, thus resulting in the formation of a polypeptide that protects against metabolic-stress-induced heart failure.
Liu et al. describe a molecular network wherein SIRT7 couples light-driven systemic body temperature cues to hepatic oscillators via HSP70 to ensure circadian phase coherence and glucose homeostasis in the liver.
Al Nabhani et al. show how excessive caloric intake during the postnatal period increases the risk of developing intestinal bowel disease during adulthood, owing to increased intestinal permeability, cytokines and hydrogen sulfide production by the microbiota.
Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.
In addition to having direct anti-cancer effects, the cardiac glycoside ouabain is shown to kill a broad range of senescent cells, thus suggesting that cardiac glycosides represent a novel class of senolytics.
Dietary restriction (DR) late in life does not improve survival and has little benefit in metabolic health in mice. The absence of a DR gene-expression signature in fat tissue suggests that a ‘nutritional memory’ interferes with the benefits of DR.
Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.
Anoxia─lack of oxygen─commonly occurs during ischaemic heart disease. Using yeast, worms and mice, Hannich et al. show that anoxia-associated tissue injury and cell death are due to accumulation of a non-canonical sphingolipid, 1-deoxydihydroceramide, that damages the cytoskeleton.
After development, adult skeletal muscle retains the capacity to regenerate by activating muscle stem cells. Here the authors demonstrate that the glycosylphosphatidylinositol-anchored membrane protein GAS1, which is induced in muscle stem cells with age, suppresses muscle regenerative capacity but can be inhibited by glial cell line-derived neurotrophic factor (GDNF).
The liver is a heterogeneous organ organized in lobules that are radially polarized. The use of single-cell spatial transcriptomics has revealed that half of hepatic genes are differentially expressed across the lobule. Ben-Moshe et al. show how a multi-omics approach, which consists of transcriptomics, micro RNA profiling and proteomics, allows for characterization of liver heterogeneity with higher resolution.
Tajima and colleagues identify mitochondrial lipoylation as a post-transcriptional molecular signature of aged brown adipose tissue (BAT) in mice. Reduced mitochondrial lipoylation is tightly coupled with the age-associated decline in BAT function, whereas enhanced lipoylation restores BAT activity in aged mice.
Chen et al. report that TGF-β signalling, although largely considered anti-inflammatory, has proinflammatory effects on endothelial cells. Inhibition of endothelial TGF-β signalling decreases atherosclerosis in mice and reverts established plaques, in part by decreasing endothelial-to-mesenchymal transitions.
Some follicular B cell lymphomas harbour activating mutations in RRAGC, activator of the nutrient sensor mTORC1. Here the authors show that these mutations confer insensitivity to nutrient deprivation and synergize with paracrine cues from the supportive T cell microenvironment to accelerate lymphomagenesis, but impose vulnerability to inhibition of mTORC1.
Folgueira et al. show that dopamine signalling in the lateral hypothalamic area and the zona incerta reduces body weight and increases energy expenditure by increasing brown adipose tissue thermogenesis in rodents. Weight loss and increased energy expenditure were also observed in patients treated with a dopamine receptor 2 agonist.
Brown adipose tissue (BAT) has high thermogenic potential and is considered a promising target to counteract obesity. Here de Jong et al. demonstrate that human BAT is more similar to classical brown than to beige adipose tissue from mice kept at thermoneutrality and challenged with a high-fat diet.